Career Summary

Biography

Dr. Rick Thorne (PhD 1999) is a postdoctoral researcher sponsored by the HMRI Cancer Research Program and contracted lecturer in the School of Biomedical Sciences & Pharmacy at the University of Newcastle.

His major interest involves different families of cell adhesion molecules and how these engage signalling pathways, particularly how these contribute to the development and progression of cancer. These interests overlap with CD36, another signalling molecule with disease functions outside cancer, particularly the metabolic syndrome and related disorders such as diabetes.

Dr. Thorne has over ten years postdoctoral experience beginning with the award of a two year competitive postdoctoral fellowship Brawn Postdoctoral Research Fellow undertaken at the UoN under Prof. Gordon Burns. During that period he was awarded two competitive overseas training schemes through the UICC, an International Cancer Technology Transfer Fellowships undertaken at the ICRF in London, UK (2000) and a Cancer Research Training Course held in Toronto, Canada (2001). Pursing further training he then relocated the UK to take up a three year post as a Postdoctoral Fellow in Training (2002-2004) at the 5* Institute of Cancer Research (ICR, London).

This appointment also led to a number of quality publications and first-hand experience as a PhD supervisor and supervisor of graduate student projects for Imperial College (honours equivalent). Following the ICR appointment he returned to UoN under an ARC Australian Postdoctoral Fellowship awarded from 2004-2007 in connection with an ARC Discovery Project. Subsequent to this award he received a three year Cancer Institute NSW fellowship for the period 2008-2010. After a number of years acting as laboratory manager for the Cancer Research Unit, Dr. Thorne inherited the facilities’ of Prof. Burns and now runs this laboratory on an independent basis.

Over the last five years Dr. Thorne has contributed 27 original research articles and one review article. For ten of these publications he is the first, equal contributory or senior author. Within this body of work there is a strong indication of productive collaborations with local, national and international colleagues.

Research ExpertiseI have been working in laboratory-based science for nearly twenty years with direct hands on experience in vast array of techniques. I have a strong interest in the technical aspects of science, and have been instrumental in obtaining key equipment for my own research work and for the greater benefit of my research colleagues.

Imaging: I have developed and manage a microscope facility consisting of a trio of three Zeiss microscopes freely available to all subject to appropriate training.

All utilise a common software package (Axiovision) that helps in training of users. I have a great deal of experience in immunofluorescence and confocal microscopic imaging. The Axioplan 2 is a standard upright miscroscope equipped with colour and monochrome cameras, Apotome imaging device, Colibri 2 illumination system. This is powerful system fitted with a large number of epifluorescence filter sets and high performance objectives. This system is adaptable to almost any specimen on a slide. The Axiovert 200 is a manual inverted fluorescence microscope fitted with a high resolution monochrome camera. Suitable for general work using cultured cells. The Cell Observer System is for live cell imaging and more complex scanning tasks. It consists of an automated inverted microscope with scanning stage and an integrated incubator system. Cell culture and in vitro assays: derivation and maintenance of cell lines, cryopreservation, mycoplasma screening, cell transfection methods, cloning and cell sorting, production and characterization of monoclonal antibodies, cell adhesion, migration and chemotaxis assays, drug toxicity, apoptosis, phagocytosis and cell-mediated immunity assays. In vivo models: I have developed experimental models for cancer metastasis and immunoscintography in human xenograft models of melanoma, and experimental chemotherapy protocols for an rodent model of acquired drug-resistance in mammary cancer.

Additionally I have sat on a number of RHD confirmation panels for students from both the School of Biological Sciences and the School of Medicine and Public Health. Honours (and equivalent) supervision Ms. Ka Man Emily Chu (Final Year Project, Imperial College London, 2003) Ms. Dale Anne Boyce (Honours, Bachelor of Biomedical Sciences, University of Newcastle, 2005) Mr. Andrew James William Weir (Honours, Bachelor of Biomedical Sciences, University of Newcastle, 2007) Mr. Simon Bone (Honours, Bachelor of Biomedical Sciences, University of Newcastle, 2007) Mr. Steven Alley (Honours, Bachelor of Biomedical Sciences, University of Newcastle, 2009) Mr. Tim Kelso (Honours, Bachelor of Biomedical Sciences, University of Newcastle, 2010) Ms. Anna Timofeeva (Final Year Project, Karolinska Institute, Sweden, 2011) Undergraduate Teaching experience Contracted 0.5 lecturing appointment for undergraduate teaching in the School of Biomedical Sciences Bachelor’s program in 2001 and 2012 where I lectured major components of HUBS 2206 (Human Biochemistry and Cell Biology), HUBS 2209 (Human Molecular Science) and supervised associated Laboratory Practical Classes Course coordinator of HUBS 3409 (Project in Biomedical Sciences) in 2011 and 2012

Administrative ExpertiseMembership of the Steering committee of the HMRI Cancer Research Program (2005-current) Organising committee member and session chairs for the HMRI Translational Cancer Conferences held in 2006 and 2008 Convener of the HMRI CRP seminar program from 2005-2009 HMRI Grant Review Panel Member 2009 Ad hoc representation on various committees at the School and Faculty level acting on behalf of Cancer Researchers and/or the discipline of Medical Biochemistry Reviewer of project grant applications in Research Infrastructure Block Grant (RIBG) Scheme (2006) Peer reviewer for both ARC Discovery and NHMRC Project grants since 2007 Peer reviewer for a number of scientific journals including Biochemical Journal, Journal of Lipid Research, Experimental Cell Research, Immunology and Cell Biology, Journal of Signal Transduction, Stem Cell Reviews & Reports and the British Journal of Cancer Member of the NHMRC GRPs in 2011 and 2012 assessing grants for Cancer Biology & Oncology

Qualifications

PhD, University of Newcastle

Bachelor of Science, University of Newcastle

Bachelor of Science (Honours), University of Newcastle

Keywords

apoptosis

cell adhesion

cell signaling

Fields of Research

Code

Description

Percentage

110199

Medical Biochemistry and Metabolomics not elsewhere classified

30

110399

Clinical Sciences not elsewhere classified

30

060199

Biochemistry and Cell Biology not elsewhere classified

40

Professional Experience

UON Appointment

Title

Organisation / Department

Academic appointment

Dates

Title

Organisation / Department

1/01/2010 - 1/12/2012

Postdoctoral Fellow and Contracted Lecturer

University of NewcastleSchool of Biomedical Sciences and PharmacyAustralia

1/01/2009 -

Membership - American Association of Cancer Research

American Association of Cancer ResearchUnited States

1/01/2008 - 1/12/2010

CI NSW Career Development Postdoctoral Fellow

University of NewcastleSchool of Biomedical Sciences and PharmacyAustralia

1/06/2004 - 1/06/2007

ARC Postdoctoral Research Fellow

University of NewcastleSchool of Biomedical Sciences and PharmacyAustralia

1/05/2001 - 1/05/2004

Postdoctoral Fellow in Training

Insititute of Cancer Research, LondonBreakthrough Breast Cancer Research CentreUnited States

1/01/2000 - 1/04/2001

Fellowship - Gladys M Brawn Memorial Fellowship

University of Newcastle

1/01/2000 - 1/05/2001

Gladys M. Brawn Postdoctoral Research Fellow

University of NewcastleSchool of Biomedical Sciences and PharmacyAustralia

Membership

Dates

Title

Organisation / Department

Lifetime Fellow of the UICC Organisation

The Union for International Cancer Control (UICC) Australia

Awards

Research Award

Year

Award

2007

Unknown

Invitations

Participant

Year

Title / Rationale

2006

Dr. A. Obaidat, Department of PharmacyOrganisation: Jordan University of Science and Technology, King Abdullah II Hospital

The immune and nociceptive systems are shaped during the neonatal period where they undergo fine-tuning and maturation. Painful experiences during this sensitive period of develop... [more]

The immune and nociceptive systems are shaped during the neonatal period where they undergo fine-tuning and maturation. Painful experiences during this sensitive period of development are known to produce long-lasting effects on the immune and nociceptive responses. It is less clear, however, whether inflammatory pain responses are primed by neonatal exposure to mild immunological stimuli, such as with lipopolysaccharide (LPS). Here, we examine the impact of neonatal LPS exposure on inflammatory pain responses, peripheral and hippocampal interleukin-1Ã (IL-1Ã), as well as mast cell number and degranulation in preadolescent and adult rats. Wistar rats were injected with LPS (0.05 mg/kg IP, Salmonella enteritidis) or saline on postnatal days (PNDs) 3 and 5 and later subjected to the formalin test at PNDs 22 and 80-97. At both time-points, and one-hour after formalin injection, blood and hippocampus were collected for measuring circulating and central IL-1Ã levels using ELISA and Western blot, respectively. Paw tissue was also isolated to assess mast cell number and degree of degranulation using Toluidine Blue staining. Behavioural analyses indicate that at PND 22, LPS-challenged rats displayed enhanced flinching (p

Infiltration of the tumor microenvironment by nerve fibers is an understudied aspect of breast carcinogenesis. In this study, the presence of nerve fibers was investigated in a co... [more]

Infiltration of the tumor microenvironment by nerve fibers is an understudied aspect of breast carcinogenesis. In this study, the presence of nerve fibers was investigated in a cohort of 369 primary breast cancers (ductal carcinomas in situ, invasive ductal and lobular carcinomas) by immunohistochemistry for the neuronal marker PGP9.5. Isolated nerve fibers (axons) were detected in 28% of invasive ductal carcinomas as compared to only 12% of invasive lobular carcinomas and 8% of ductal carcinomas in situ (p=0.0003). In invasive breast cancers, the presence of nerve fibers was observed in 15% of lymph node negative tumors and 28% of lymph node positive tumors (p=0.0031), indicating a relationship with the metastatic potential. In addition, there was an association between the presence of nerve fibers and the expression of nerve growth factor (NGF) in cancer cells (p=0.0001). Invitro, breast cancer cells were able to induce neurite outgrowth in PC12 cells, and this neurotrophic activity was partially inhibited by anti-NGF blocking antibodies. In conclusion, infiltration by nerve fibers is a feature of the tumor microenvironment that is associated with aggressiveness and involves NGF production by cancer cells. The potential participation of nerve fibers in breast cancer progression needs to be further considered.

Nerve infiltration is essential to prostate cancer progression, but the mechanism by which nerves are attracted to prostate tumors remains unknown. We report that the precursor of... [more]

Nerve infiltration is essential to prostate cancer progression, but the mechanism by which nerves are attracted to prostate tumors remains unknown. We report that the precursor of nerve growth factor (proNGF) is overexpressed in prostate cancer and involved in the ability of prostate cancer cells to induce axonogenesis. A series of 120 prostate cancer and benign prostate hyperplasia (BPH) samples were analyzed by IHC for proNGF. ProNGF was mainly localized in the cytoplasm of epithelial cells, with marked expression in cancer compared with BPH. Importantly, the proNGF level positively correlated with the Gleason score (n = 104, tB = 0.51). A higher level of proNGF was observed in tumors with a Gleason score of =8 compared with a Gleason score of 7 and 6 (P < 0.001). In vitro, proNGF was detected in LNCaP, DU145, and PC-3 prostate cancer cells and BPH-1 cells but not in RWPE-1 immortalized nontumorigenic prostate epithelial cells or primary normal prostate epithelial cells. Co-culture of PC12 neuronal-like cells or 50B11 neurons with PC-3 cells resulted in neurite outgrowth in neuronal cells that was inhibited by blocking antibodies against proNGF, indicating that prostate cancer cells can induce axonogenesis via secretion of proNGF. These data reveal that ProNGF is a biomarker associated with high-risk prostate cancers and a potential driver of infiltration by nerves.

Elucidation of the molecular mechanisms by which 5-fluorouracil (5-FU) induces apoptosis is required in order to understand the resistance of colorectal cancer (CRC) cells to 5-FU... [more]

Elucidation of the molecular mechanisms by which 5-fluorouracil (5-FU) induces apoptosis is required in order to understand the resistance of colorectal cancer (CRC) cells to 5-FU. In the current study, 5-FU-induced apoptosis was assessed using the propidium iodide method. Involvement of protein kinase C (PKC) was assessed by evaluating the extent of their activation in CRC, following treatment with 5-FU, using biochemical inhibitors and western blot analysis. The results revealed that 5-FU induces varying degrees of apoptosis in CRC cells; HCT116 cells were identified to be the most sensitive cells and SW480 were the least sensitive. In addition, 5-FU-induced apoptosis was caspase-dependent as it appeared to be initiated by caspase-9. Furthermore, PKCe was marginally expressed in CRC cells and no changes were observed in the levels of cleavage or phosphorylation following treatment with 5-FU. The treatment of HCT116 cells with 5-FU increased the expression, phosphorylation and cleavage of PKCd. The inhibition of PKCd was found to significantly inhibit 5-FU-induced apoptosis. These results indicated that 5-FU induces apoptosis in CRC by the activation of PKCd and caspase-9. In addition, the levels of PKCd activation may determine the sensitivity of CRC to 5-FU.

Background: Macrophage migration inhibitory factor (MIF) is a widely expressed cytokine involved in a variety of cellular processes including cell cycle regulation and the control... [more]

Background: Macrophage migration inhibitory factor (MIF) is a widely expressed cytokine involved in a variety of cellular processes including cell cycle regulation and the control of proliferation. Overexpression of MIF has been reported in a number of cancer types and it has previously been shown that MIF is upregulated in melanocytic tumours with the highest expression levels occurring in malignant melanoma. However, the clinical significance of high MIF expression in melanoma has not been reported. Methods: MIF expression was depleted in human melanoma cell lines using siRNA-mediated gene knockdown and effects monitored using in vitro assays of proliferation, cell cycle, apoptosis, clonogenicity and Akt signalling. In silico analyses of expression microarray data were used to correlate MIF expression levels in melanoma tumours with overall patient survival using a univariate Cox regression model. Results: Knockdown of MIF significantly decreased proliferation, increased apoptosis and decreased anchorage-independent growth. Effects were associated with reduced numbers of cells entering S phase concomitant with decreased cyclin D1 and CDK4 expression, increased p27 expression and decreased Akt phosphorylation. Analysis of clinical outcome data showed that MIF expression levels in primary melanoma were not associated with outcome (HR = 1.091, p = 0.892) whereas higher levels of MIF in metastatic lesions were significantly associated with faster disease progression (HR = 2.946, p = 0.003 and HR = 4.600, p = 0.004, respectively in two independent studies). Conclusions: Our in vitro analyses show that MIF functions upstream of the PI3K/Akt pathway in human melanoma cell lines. Moreover, depletion of MIF inhibited melanoma proliferation, viability and clonogenic capacity. Clinically, high MIF levels in metastatic melanoma were found to be associated with faster disease recurrence. These findings support the clinical significance of MIF signalling in melanoma and provide a strong rationale for both targeting and monitoring MIF expression in clinical melanoma.